Immune responses against multiple epitopes: a theory for immunodominance and antigenic variation

A simple and natural model for the nonlinear interaction between the immune system and multiple epitopes of a genetically variable pathogen can explain the main features of the complex phenomenon of immunodominance. In this model, antigenically homogeneous populations of pathogens stimulate an immunodominant response against a single epitope. In contrast, a heterogeneous pathogen population induces a dynamically complicated array of fluctuating responses against multiple epitopes. Antigenic escape in one epitope can shift immunodominance to other, potentially weaker, epitopes, thereby altering the selective pressures on the pathogen population as a whole. These ideas are compared with detailed studies of the shifting patterns of antigenic variation and cytotoxic T-cell responses seen in HIV-1 infected patients.